Journal
JOURNAL OF CONTROLLED RELEASE
Volume 155, Issue 2, Pages 303-311Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2011.07.009
Keywords
Non-viral gene delivery; Polyplex; Peptide copolymer; HPMA; RAFT polymerization
Funding
- NINDS NIH HHS [R01 NS064404, R01 NS064404-03, NIH/NINDS1R01 NS064404] Funding Source: Medline
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Polycations are one of the most frequently used classes of materials for non-viral gene transfer in vivo. Several studies have demonstrated a sensitive relationship between polymer structure and delivery activity. In this work, we used reverse addition-fragmentation chain transfer (RAFT) polymerization to build a panel of N-(2-hydroxypropyl)methacrylamide (HPMA)-oligolysine copolymers with varying peptide length and polymer molecular weight. The panel was screened for optimal DNA-binding, colloidal stability in salt, high transfection efficiency, and low cytotoxicity. Increasing polyplex stability in PBS correlated with increasing polymer molecular weight and decreasing peptide length. Copolymers containing K-5 and K-10 oligocations transfected cultured cells with significantly higher efficiencies than copolymers of K-15. Four HPMA-oligolysine copolymers were identified that met the desired criteria. Polyplexes formed with these copolymers demonstrated both salt stability and transfection efficiencies on-par with poly(ethylenimine) PEI in cultured cells. (C) 2011 Elsevier B.V. All rights reserved.
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